1. The Field of the Invention
This invention relates to increasing the spatial selectivity and/or sensitivity of spectroscopic measurements, for example as can be used to make non-invasive measurements of analytes in biological organisms.
2. Background and Relevant Art
Many attempts have been made to create appropriate apparatus for the non-invasive measurement of significant substances within biological organisms. The importance of such measurement capability arises not only from the need to observe biochemical reactions in such organisms without disturbance to the system but also in order to help control chronic diseases such as diabetes, where it is highly desirable to measure the patients blood glucose levels much more frequently than is practical, when puncturing the skin is required. Molecular spectroscopy has been proposed to make such measurements; however, the blood and interstitial fluids contain a very great number of compounds which must be distinguished. Absorption spectroscopy in the visible or near infrared suffers from the difficulty that the spectrum of many compounds that are present in the blood and other tissues substantially overlap in this region. Mid-IR spectroscopy produces spectra which are considerably more unique to individual molecules but suffers from two serious problems: (1) Detectors must be operated at very cold temperatures if they are to be sufficiently sensitive and (2) Water absorbs mid-IR radiation very strongly and such radiation can only penetrate a few tens of microns into an organism.
Raman spectroscopy has been proposed to obviate some of these difficulties. In Raman spectroscopy a scattering spectrum is produced, at frequencies which are at the difference of the input radiation, and the characteristic spectral frequencies of the molecule. The resulting spectral signatures are advantageously particular to the analytes of interest. However, the cross-sections for Raman scattering are very small, and the resulting signals are very weak. Weak signals can also arise from spectroscopies that use other non-linear processes, or where the available power from the light source is small. Other representative examples would include four wave mixing, frequency doubling, and multiphoton fluorescence.
The difficulties arising from the weakness of the signal can be greatly exacerbated if the analyte of interest is primarily located at some depth away from and/or below the surface of the sample, and if the sample otherwise produces a large amount of scattering of the optical signal (turbid medium). A further complication arises when the material, which comprises the layers that are near the surface, consists of compounds whose spectra have substantial overlap with that of the analyte. Even if the aperture of the optical system which collects the light is large, the signal of interest may be dominated by the compounds near the surface, and the signal produced by the analyte will be obscured. A large optical aperture for the system will inevitably give rise to large optical collecting elements such as lenses or mirrors whose function is to separate light having a multiplicity of optical wavelengths into its constituent spectral components. The size of and cost of the whole apparatus will therefore scale positively with the aperture size.